Intelligent manufacturing equipment and method of multi-domain organism targeted nutritional protective composite preparation
By introducing position adjustment and axis limiting components into intelligent manufacturing equipment, the alignment deviation and vibration problems of microfluidic sampling needles were solved, enabling precise sampling and efficient biochemical analysis of multi-biological targeted nutritional protection compound preparations.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- CHANGSHA UNIVERSITY OF SCIENCE AND TECHNOLOGY
- Filing Date
- 2026-04-15
- Publication Date
- 2026-07-10
AI Technical Summary
Existing intelligent manufacturing equipment for multi-biological targeted nutritional protection compound preparations suffers from problems such as inaccurate sampling volume and sample leakage caused by misalignment of microfluidic sampling needles and sampling holes and vibration, which affect biochemical analysis results.
Employing a position adjustment component and an axis limiting component, the microfluidic sampling needle is precisely installed and guided through the cooperation of an electromagnet and a magnetic block. Combined with the clamping of the guide tube and the elastic ring, deviation and vibration are avoided, ensuring sampling accuracy.
It effectively avoids the alignment deviation and vibration effects of microfluidic sampling needles during the sampling process, ensuring accurate and leak-free sampling, and improving the reliability and accuracy of biochemical analysis.
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Figure CN122352385A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of bio-intelligent manufacturing technology, and in particular to an intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation. Background Technology
[0002] Biomanufacturing is a green and low-carbon technology that uses industrial biotechnology as its core and employs genetic engineering, synthetic biology, and other methods to process and transform materials through organisms such as microorganisms, enzymes, or cells. For example, in the field of enzyme engineering, by rationally designing and modifying enzyme proteins, green and efficient new biosynthetic pathways have been developed, which can catalyze the formation of amide bonds under mild conditions, providing new solutions for the biomanufacturing of products such as drugs.
[0003] Intelligent manufacturing is a human-machine integrated intelligent system composed of intelligent machines and human experts. It can perform intelligent activities during the manufacturing process, such as analysis, reasoning, judgment, conception, and decision-making. Based on the development of intelligent manufacturing, it can be applied to biomanufacturing, providing convenience for bio-intelligent manufacturing.
[0004] Most existing intelligent manufacturing equipment for multi-biological targeted nutritional protection compound preparations typically involves the following steps: First, an AI model designs and screens high-affinity cross-biological active candidate molecules based on the target requirements of the actual application. Then, based on molecular characteristics and application scenarios, nanocarriers or multilayer capsules with targeting and responsive release functions are precisely prepared. During the preparation process, online monitoring is used to correct process deviations in real time to ensure product quality. Subsequently, multi-organ chip simulations of the microenvironment of four biological species are used to verify the actual biological effects of the preparation. Finally, the data from the entire process is integrated to retrain the AI model and digital twin model, enabling the next round of design and manufacturing optimization, thus forming an intelligent manufacturing cycle with self-evolutionary capabilities.
[0005] However, when verifying the actual biological effects of the formulation, the above methods generally use microfluidic sampling needles, ELISA analysis modules, and mass spectrometers. The microfluidic sampling needle needs to accurately sample at the outlet of the multi-organ chip according to preset instructions. However, long-term high-frequency micron-level reciprocating motion and vibration generated by the overall operation of the equipment may cause alignment deviation between the microfluidic sampling needle and the sampling orifice, resulting in inaccurate sampling volume, sample leakage, and affecting the biochemical analysis results.
[0006] Therefore, the present invention provides an intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation to solve the above problems. Summary of the Invention
[0007] The purpose of this invention is to overcome the shortcomings of the prior art and to propose an intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation.
[0008] To achieve the above objectives, the present invention adopts the following technical solution: A smart manufacturing equipment for a multi-biological targeted nutritional protection compound preparation includes: a manufacturing shell, wherein the interior of the manufacturing shell is equipped with an AI molecular design and virtual screening unit, an intelligent targeted delivery system preparation unit, a multi-scale online quality monitoring module, a four-biological effect simulation and verification unit, and a central control and digital twin server. Among them, the components of the four-dimensional biological effect simulation and verification unit include a multi-organ chip array, an automated biochemical analyzer, and a fine-tuning module; The multi-organ chip array is provided with sampling holes; The fine-tuning module includes a position adjustment component and an axis limiting component; The position adjustment component includes a mounting slot formed on a multi-organ chip array. Elastic positioning rods are symmetrically arranged inside the mounting slot. A movable plate is attached to the upper surface of the elastic positioning rod. Movable frames are attached to both sides of the two movable plates. A pull plate is snapped onto the surface of the two movable frames. A threaded rod is threadedly connected to the surface of the pull plate. A drive source is provided on one side of the threaded rod. A pointer is fixedly connected to the surface of the movable frame.
[0009] Preferably, the position adjustment assembly further includes magnet blocks fixedly connected to both sides of the lower surface of the movable plate. The lower surface of the magnet blocks is fitted with electromagnets connected to an external power source, and the electromagnets are fixedly connected in a rectangular array inside the mounting groove. Based on the setting of the elastic positioning rod, the electromagnets and magnet blocks remain parallel during installation.
[0010] Preferably, the position adjustment component further includes a magnifying glass disposed above the pull plate and perpendicular to the pointer. A scale plate is fixedly connected to one side of the magnifying glass for magnifying the pointer and the scale on the scale plate. A support frame is fixedly connected to one side of the scale plate, and the moving plate is fixedly connected to the support frame.
[0011] Preferably, the axis limiting assembly includes a guide box fixedly connected to one side of the support frame. The guide box has radial fine-tuning rollers evenly arranged longitudinally inside. The guide box also has a sliding block that slides inside the guide box and fits against the radial fine-tuning rollers. The sliding block is made of elastic material and is used to fit tightly against the inner wall of the guide box.
[0012] Preferably, the axis limiting assembly further includes a microfluidic sampling needle fitted inside the sliding block and connected to the automated biochemical analyzer. The surface of the microfluidic sampling needle is fitted with a guide tube, and an elastic ring that fits tightly against the outer arc surface of the microfluidic sampling needle is fixedly connected inside the guide tube. The guide tube is fixedly connected to the support frame.
[0013] Preferably, the axis limiting assembly further includes a damping spring assembly that fits against the lower surface of the sliding block. The lower surface of the damping spring assembly is fixedly connected to the guide tube, and one side of the damping spring assembly is fixedly connected to an electric push rod that is fixedly connected to the support frame, for driving the reciprocating motion of the sliding block and the microfluidic sampling needle.
[0014] Preferably, a rubber sealing gasket is fixedly connected to one side of the upper surface of the support frame and is coaxially arranged with the microfluidic sampling needle. The microfluidic sampling needle can penetrate the rubber sealing gasket and the support frame to pierce into the multi-organ chip array for sampling.
[0015] Preferably, the AI molecular design and virtual screening unit includes a high-throughput molecular synthesis module and an automated molecular interaction analysis module; Among them, the high-throughput molecular synthesis module contains multiple parallel microreactor arrays, each microreactor being connected to multiple precursor compound tanks, used to automatically synthesize candidate antimicrobial peptide molecules generated by AI models under the instructions of the central control system; Automated molecular interaction analysis module: A microfluidic chip equipped with a surface plasmon resonance sensor is used to automatically detect the binding kinetic constants of candidate molecules and multi-boundary biological target proteins pre-immobilized in the chip channels; The intelligent targeted delivery system fabrication unit includes a multi-channel microfluidic chip fabrication platform and a 3D printing multi-layer capsule molding module. Among them, the multi-channel microfluidic chip fabrication platform includes a replaceable microfluidic chip, on which multiple micromixers and microreaction chambers are integrated. The platform is connected to the carrier material storage tank and the core molecule storage tank through a precision injection pump and a pressure controller. 3D Printing Multilayer Capsule Molding Module: Includes a coaxial 3D bioprinter, used to print prepared nanocarriers and hydrogel materials with different pH responses into composite formulations with multilayer structures according to a preset 3D model.
[0016] Preferably, the multi-scale online quality monitoring module includes an online particle size and potential analyzer and a process analysis technology system; Among them, by connecting the flow cell to the outlet of the microfluidic chip fabrication platform, the particle size distribution and zeta potential of the fabricated nanocarrier are monitored in real time using the principle of dynamic light scattering; Process analysis technology system: includes multiple near-infrared spectral probes installed in key locations such as microfluidic chips and mixing vessels to monitor changes in chemical composition during the reaction process in real time; The multi-organ chip array includes parallel microfluidic cell culture chips that respectively simulate human intestinal epithelium, plant leaf microenvironment, and soil microbial community. The chips are equipped with pH and dissolved oxygen sensors. The automated biochemical analyzer automatically collects samples from the outlet of the multi-organ chip array via a microfluidic sampling needle and connects to the built-in ELISA analysis module for detecting cytokines and metabolites. The central control and digital twin server includes a high-performance computing server on which digital twin models and AI algorithms run. The server is connected to the sensors and actuators of all the above-mentioned units via data cables, forming a complete industrial Internet of Things system.
[0017] A method for intelligent manufacturing equipment of a multi-biological targeted nutritional protection compound preparation, applied to the intelligent manufacturing equipment of the multi-biological targeted nutritional protection compound preparation described in any one of the above-mentioned methods, includes the following steps: Step S1: Molecular design and virtual screening: The central control system calls the internally pre-trained GAN-Transformer model to generate a set of candidate antimicrobial peptide sequences based on the input target requirements. Control commands are sent to the AI molecular design and virtual screening unit to start the high-throughput molecular synthesis module and the automated molecular interaction analysis module, to perform rapid synthesis and binding kinetics verification of candidate molecules, and to screen out the top N molecules with the highest affinity. Step S2: Design and manufacture of the targeted delivery system: The central control system, based on the selected molecule and the preset application scenario, calls the formulation parameters in the database to determine the carrier type and particle size target; Control commands are sent to the intelligent targeted delivery system fabrication unit to adjust the flow rate ratio and mixing time of each channel of the multi-channel microfluidic chip fabrication platform, and to fabricate nanocarriers loaded with target molecules online. If a multi-layer structure is required, the 3D printing multi-layer capsule molding module is activated to print the nanocarrier and responsive material together. Step S3: Online quality monitoring and closed-loop feedback: The prepared nanocarrier suspension was passed through an online particle size and potential analyzer of a multi-scale online quality monitoring module; If the detected particle size distribution (PDI) is greater than 0.12 or the encapsulation rate is lower than the threshold, the central control system adjusts the flow rate or formulation ratio of the microfluidic chip in real time until the product quality is qualified, thus achieving closed-loop control. Step S4: Simulation and Verification of Biological Effects in the Four Realms Qualified formulation samples are automatically or manually introduced into the corresponding multi-organ on-chip array of the Four Boundary Biological Effects Simulation and Validation Unit; The automated biochemical analyzer automatically samples at preset time points to analyze key biomarkers in the chip's microenvironment; Step S5: Data Integration and Model Iteration The central control system integrates all the data generated in steps S1 to S4 and stores it in the database. Using this data, the digital twin model and reinforcement learning model in the central control server are retrained to optimize the next molecular design scheme and process parameters, achieving intelligent iteration throughout the entire process.
[0018] Compared with the prior art, the beneficial effects of the present invention are: 1. Based on the collaboration of multiple components in the fine-tuning module, when the device samples materials in the multi-organ chip array through microfluidic sampling, the electromagnet is energized to generate magnetic force, which tightly attracts the magnet block, and the support frame is installed on the elastic positioning rod to achieve precise installation of the microfluidic sampling needle and avoid initial alignment deviation during the installation process. 2. When the microfluidic sampling needle reciprocates repeatedly and other components vibrate during use, causing the microfluidic sampling needle to deviate from the support frame, the pointer slides on the surface of the scale plate, and the deviation distance is magnified and displayed through a magnifying glass. Then, the drive source is activated to drive the threaded rod to rotate, which drives the pull plate to move left and right, thereby pushing the moving frame, moving plate, and magnetic block to slide on the electromagnet, thereby adjusting the position of the support frame and the microfluidic sampling needle, so that the pointer returns to the initial position, avoiding the problem of inaccurate sampling and sample leakage caused by the alignment deviation between the microfluidic sampling needle and the sampling hole during use; 3. Based on the synergy of multiple components in the axial constraint assembly, this device guides the microfluidic sampling needle as it reciprocates in the sampling hole via an electric push rod to collect and deliver the material for testing. The guide tube and radial fine-tuning rollers guide the microfluidic sampling needle, while an elastic ring clamps it, ensuring it remains coaxial with the guide tube. This prevents deviation during sampling. Furthermore, the tight fit between the sliding block and the inner wall of the guide box, along with the damping spring assembly, prevents radial movement of the sliding block within the guide box, thus avoiding any impact on the radial position of the microfluidic sampling needle. The reciprocating motion of the sliding block is also buffered, preventing significant vibration during movement that could affect the sampling accuracy of the microfluidic sampling needle. Attached Figure Description
[0019] Figure 1 This is a front structural schematic diagram of the intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation proposed in this invention. Figure 2 This is a schematic diagram of the internal structure of the intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation proposed in this invention. Figure 3This is a schematic diagram of the intelligent targeted delivery system preparation unit and the four-world biological effect simulation and verification unit of the intelligent manufacturing equipment and method for a multi-world biological targeted nutritional protection compound preparation proposed in this invention. Figure 4 This is a schematic diagram of the multi-scale online quality monitoring module and the four-sphere biological effect simulation and verification unit structure of the intelligent manufacturing equipment and method for a multi-sphere biological targeted nutritional protection compound preparation proposed in this invention. Figure 5 This is a schematic diagram of the structure of a multi-organ chip array and fine-tuning module for an intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation proposed in this invention. Figure 6 This is a schematic diagram of the fine-tuning module and multi-organ chip structure of the intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation proposed in this invention. Figure 7 This is a schematic diagram of the fine-tuning module structure of an intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation proposed in this invention. Figure 8 This is a schematic diagram of the position adjustment component and the axis limiting component of the intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation proposed in this invention. Figure 9 This is a schematic diagram showing the disassembled structure of the position adjustment component and the axis restriction component of the intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation proposed in this invention. Figure 10 This is a schematic diagram of the support frame and axis constraint component structure of the intelligent manufacturing equipment and method for a multi-biological targeted nutritional protection compound preparation proposed in this invention.
[0020] In the diagram: 1. Manufacturing shell; 2. Mounting slot; 3. Elastic positioning rod; 4. Moving plate; 5. Moving frame; 6. Pulling plate; 7. Threaded rod; 8. Pointer; 9. Magnet block; 10. Electromagnet; 11. Magnifying glass; 12. Scale plate; 13. Support frame; 14. Guide box; 15. Radial fine-tuning roller; 16. Sliding block; 17. Microfluidic sampling needle; 18. Guide tube; 19. Elastic ring; 20. Damping spring assembly; 21. Electric push rod; 22. Rubber sealing gasket; 23. AI molecular design and virtual screening unit; 24. Intelligent targeted delivery system preparation unit; 25. Central control and digital twin server; 26. Four-dimensional biological effect simulation and verification unit. Detailed Implementation
[0021] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.
[0022] The terms used in this invention, such as "upper," "lower," "left," "right," "middle," and "one," are merely for clarity of description and are not intended to limit the scope of the invention. Any changes or adjustments to their relative relationships, without substantially altering the technical content, should also be considered within the scope of the invention.
[0023] Reference Figures 1-10 A smart manufacturing equipment for a multi-biological targeted nutritional protection compound preparation includes: a manufacturing shell 1, the interior of which is equipped with an AI molecular design and virtual screening unit 23, an intelligent targeted delivery system preparation unit 24, a multi-scale online quality monitoring module, a four-biological effect simulation and verification unit 26, and a central control and digital twin server 25. Among them, the 26 components of the Four Realms Biological Effect Simulation and Verification Unit include a multi-organ chip array, an automated biochemical analyzer, and a fine-tuning module; The multi-organ-on-a-chip array has sampling holes; The fine-tuning module includes a position adjustment component and an axis limiting component; The position adjustment component includes a mounting slot 2 opened on the multi-organ chip array. Elastic positioning rods 3 are symmetrically arranged inside the mounting slot 2. A movable plate 4 is attached to the upper surface of the elastic positioning rod 3. Movable frames 5 are attached to both sides of the two movable plates 4. Pulling plates 6 are snapped onto the surfaces of the two movable frames 5. A threaded rod 7 is threadedly connected to the surface of the pull plate 6. A drive source is provided on one side of the threaded rod 7. A pointer 8 is fixedly connected to the surface of the movable frame 5. The support frame 13 is sleeved onto the elastic positioning rod 3, and the fine-tuning module is installed inside the mounting slot 2 to achieve precise installation of the microfluidic sampling needle 17 and avoid deviations during installation that could lead to subsequent alignment deviations with the sampling hole. Furthermore, based on the setting of the elastic positioning rod 3, it is more convenient to install the support frame 13, and it will not require multiple alignments because the diameter of the positioning rod is similar to the mounting hole set on the support frame 13; The drive source includes a motor, two meshing gears and a protective box. One gear is fixedly connected to the output end of the motor, and the other gear is fixedly connected to the threaded rod 7. The motor is fixedly installed inside the protective box, the gear is rotatably installed in the protective box, and the threaded rod 7 is rotatably connected to the protective box to drive the threaded rod 7 to rotate, thereby driving the pull plate 6 and the moving frame 5 to move. The position adjustment assembly also includes a magnifying glass 11 disposed above the pull plate 6 and perpendicular to the pointer 8. A scale plate 12 is fixedly connected to one side of the magnifying glass 11 for magnifying the pointer 8 and the scale on the scale plate 12. A support frame 13 is fixedly connected to one side of the scale plate 12, and the moving plate 4 is fixedly connected to the support frame 13. A photoelectric sensor is added at the scale plate 12. The photoelectric sensor is existing technology. It monitors the offset of pointer 8 and quantifies the deviation trigger threshold. The adjustment is initiated when the pointer offset is 0.01mm. The sensor is linked with the central control system and the drive source to realize automatic adjustment. Furthermore, the lead of the threaded rod has a transmission accuracy of 0.5mm; The motor is connected to the central control and digital twin server 25 to monitor the position of pointer 8 on scale plate 12 in real time; The support frame 13 is provided with mounting holes with a diameter similar to that of the elastic positioning rod 3; Reference Figure 8 and Figure 9 The position adjustment assembly also includes magnet blocks 9 fixedly connected to both sides of the lower surface of the movable plate 4. The lower surface of the magnet blocks 9 is attached to an electromagnet 10 connected to an external power source, and the electromagnets 10 are fixedly connected in a rectangular array inside the mounting groove 2. Based on the setting of the elastic positioning rod 3, the electromagnets 10 and the magnet blocks 9 remain parallel during installation. The surface of the electromagnet 10 is coated with a polytetrafluoroethylene anti-friction coating, and the electromagnet 10 adjusts the attraction force by current. When fixed, the attraction force is high with high current and low with low current when adjusted. It does not hinder sliding under low current conditions. In the embodiments of the above technical solution, when sampling materials in the multi-organ chip array through the microfluidic sampling needle 17, the electromagnet 10 is energized to generate magnetic force, which is tightly attracted to the magnet block 9, and the support frame 13 is installed on the elastic positioning rod 3 to achieve precise installation of the microfluidic sampling needle 17 and avoid deviations during installation that could lead to subsequent alignment deviations with the sampling hole. When the microfluidic sampling needle 17 reciprocates repeatedly, and vibrations generated during the use of other components cause the microfluidic sampling needle 17 to deviate from the support frame 13, the pointer 8 slides on the surface of the scale plate 12, and the deviation distance is magnified and displayed by the magnifying glass 11, making it easier to check the deviation distance. In addition, the pointer 8 is monitored in real time by the photoelectric sensor. When the deviation of the pointer 8 is greater than 0.01mm, the central control system automatically starts the drive source, which drives the threaded rod 7 to rotate, causing the pull plate 6 to move left and right, thereby pushing the moving frame 5, the moving plate 4, and the magnet block 9 to slide on the electromagnet 10, thereby adjusting the position of the support frame 13 and the microfluidic sampling needle 17, so that the pointer 8 is reset to the initial position, and the microfluidic sampling needle 17 is reset to the initial installation position. This avoids the problem of inaccurate sampling and sample leakage caused by the alignment deviation between the microfluidic sampling needle 17 and the sampling hole during use. Furthermore, through the arrangement of the magnet block 9 and the electromagnet 10, when the microfluidic sampling needle 17 is installed, the electromagnet 10 is energized to generate magnetic force, which is tightly attracted to the magnet block 9, limiting the movement of the moving frame 5 and the moving plate 4, making them more stable after installation. When adjusting the position of the microfluidic sampling needle 17, the pull plate 6 drives the moving frame 5, the moving plate 4 and the magnet 9 to move on the electromagnet 10 to adjust the position of the microfluidic sampling needle 17. The electromagnet 10 will not obstruct its movement. After the adjustment is completed, the attraction between the electromagnet 10 and the magnet 9 restricts the microfluidic sampling needle 17 again, making it more stable during use. Reference Figure 9 and Figure 10 The axis limiting assembly includes a guide box 14 fixedly connected to one side of the support frame 13. Radial fine-tuning rollers 15 are evenly arranged longitudinally inside the guide box 14. A sliding block 16 that is in contact with the radial fine-tuning rollers 15 is slidably connected inside the guide box 14. The sliding block 16 is made of elastic material and is used to fit tightly against the inner wall of the guide box 14. The guide box 14 is used to guide the sliding block 16, and the radial fine-tuning roller 15 is used to change the sliding friction between the sliding block 16 and the guide box 14 into rolling friction, thereby reducing friction and vibration during the sliding process of the sliding block 16, and avoiding large vibration and radial offset of the microfluidic sampling needle 17 during reciprocating motion. The sliding block 16 is made of elastic rubber to ensure that the sliding block 16 fits tightly against the inner wall of the guide box 14, and to prevent the sliding block 16 from undergoing radial displacement inside the guide box 14, which would affect the radial position of the microfluidic sampling needle 17. The axial limiting assembly also includes a microfluidic sampling needle 17 fitted inside the sliding block 16 and connected to the automated biochemical analyzer. A guide tube 18 is sleeved on the surface of the microfluidic sampling needle 17, and an elastic ring 19 that fits tightly against the outer arc surface of the microfluidic sampling needle 17 is fixedly connected inside the guide tube 18. The guide tube 18 is fixedly connected to the support frame 13. The microfluidic sampling needle 17 is used to be inserted into the sampling hole to sample the material in the multi-organ chip; The guide tube 18 and the elastic ring 19 are used to guide the movement of the microfluidic sampling needle 17 and maintain its attitude; When the microfluidic sampling needle 17 reciprocates in the sampling hole based on the electric push rod 21 to collect material and send it out for testing, the microfluidic sampling needle 17 is guided by the guide tube 18 and the radial fine-tuning roller 15. At the same time, the microfluidic sampling needle 17 is clamped by the elastic ring 19 to keep it coaxial with the guide tube 18, thereby avoiding deviation of the microfluidic sampling needle 17 during sampling. The axis limiting assembly also includes a damping spring assembly 20 that fits against the lower surface of the sliding block 16. The lower surface of the damping spring assembly 20 is fixedly connected to the guide tube 18, and an electric push rod 21 that is fixedly connected to the support frame 13 is fixedly connected to one side of the damping spring assembly 20 for driving the reciprocating motion of the sliding block 16 and the microfluidic sampling needle 17. The damping spring assembly 20 includes two mounting pads that are fixedly connected to the sliding block 16 and the guide tube 18 respectively, and a damping spring that is fixedly connected to the opposite side of the two mounting pads. During the reciprocating movement of the sliding block 16 driven by the electric push rod 21, the sliding block 16 squeezes the mounting pad and the damping spring, causing them to compress and then stretch. This indirectly buffers the sliding of the sliding block 16 and absorbs the vibration generated during the movement of the sliding block 16, reducing the vibration force transmitted to the microfluidic sampling needle 17. This further prevents the microfluidic sampling needle 17 from generating large vibrations during the sampling process, which would affect the sampling of the microfluidic sampling needle 17. Reference Figure 7 and Figure 9 A rubber sealing gasket 22, which is coaxially arranged with the microfluidic sampling needle 17, is fixedly connected to one side of the upper surface of the support frame 13. The microfluidic sampling needle 17 can penetrate the rubber sealing gasket 22 and the support frame 13 to pierce the inside of the multi-organ chip array for sampling. With the rubber sealing gasket 22 in place, the microfluidic sampling needle 17 pierces and penetrates the rubber sealing gasket 22, and is inserted into the sampling hole to sample the material. When the microfluidic sampling needle 17 enters and exits, the rubber sealing gasket 22, based on its own elasticity, always tightly clamps the microfluidic sampling needle 17. This not only cleans the needle but also prevents external dust from entering the sampling hole and contaminating the material inside the multi-organ chip. Reference Figures 1-3 The AI molecular design and virtual screening unit 23 includes a high-throughput molecular synthesis module and an automated molecular interaction analysis module. Among them, the high-throughput molecular synthesis module contains multiple parallel microreactor arrays, each microreactor being connected to multiple precursor compound tanks, used to automatically synthesize candidate antimicrobial peptide molecules generated by AI models under the instructions of the central control system; Automated molecular interaction analysis module: A microfluidic chip equipped with a surface plasmon resonance sensor is used to automatically detect the binding kinetic constants of candidate molecules and multi-boundary biological target proteins pre-immobilized in the chip channels; The intelligent targeted delivery system fabrication unit 24 includes a multi-channel microfluidic chip fabrication platform and a 3D printing multilayer capsule molding module; Among them, the multi-channel microfluidic chip fabrication platform includes a replaceable microfluidic chip, on which multiple micromixers and microreaction chambers are integrated. The platform is connected to the carrier material storage tank and the core molecule storage tank through a precision injection pump and a pressure controller. 3D Printing Multilayer Capsule Molding Module: Includes a coaxial 3D bioprinter, used to print prepared nanocarriers and hydrogel materials with different pH responses into composite formulations with multilayer structures according to a preset 3D model; The multi-scale online quality monitoring module includes an online particle size and potential analyzer and a process analysis technology system; Among them, by connecting the flow cell to the outlet of the microfluidic chip fabrication platform, the particle size distribution and zeta potential of the fabricated nanocarrier are monitored in real time using the principle of dynamic light scattering; Process analysis technology system: includes multiple near-infrared spectral probes installed in key locations such as microfluidic chips and mixing vessels to monitor changes in chemical composition during the reaction process in real time; Multi-organ on-chip array: including parallel microfluidic cell culture chips that respectively simulate human intestinal epithelium, plant leaf microenvironment, and soil microbial community; pH and dissolved oxygen sensors are integrated on the chip. Automated biochemical analyzer: It automatically collects samples from the outlet of the multi-organ chip array via a microfluidic sampling needle 17 and connects to the built-in ELISA analysis module for the detection of cytokines and metabolites; The central control and digital twin server 25 includes a high-performance computing server on which a digital twin model and AI algorithms run. The server is connected to the sensors and actuators of all the above units via data cables to form a complete industrial Internet of Things system. Full-process automation and intelligent closed loop: For the first time, molecular AI design, microfluidic precision manufacturing, online quality control and organ-on-a-chip effect verification are integrated into one set of equipment, realizing an automated closed loop from virtual design to physical manufacturing and effect verification, which greatly shortens the R&D cycle; Achieving precise fabrication through design-as-manufacturing: Through the linkage and feedback between the online quality monitoring module and the microfluidic platform, process deviations can be corrected in real time, ensuring high consistency between batches of nanocarriers with RSD < 5%, truly translating design parameters into product attributes precisely; Multi-boundary biological effect co-screening: The integrated multi-organ on-chip array allows for the parallel evaluation of the diverse effects of formulations on humans, animals, plants and microorganisms on the same equipment, and can efficiently screen cross-boundary signaling molecules such as lotusine, providing a powerful engineering platform for the development of comprehensive health management solutions; It possesses self-evolution capabilities: through the mining and learning of data from the entire process by the central control system, the equipment can continuously optimize its internal AI model, making subsequent molecular design and process parameters more accurate and efficient, thus forming a continuous technological barrier.
[0024] A method for intelligent manufacturing equipment of a multi-biological targeted nutritional protection compound preparation, applied to the intelligent manufacturing equipment of the multi-biological targeted nutritional protection compound preparation described in any one of the above-mentioned methods, includes the following steps: Step S1: Molecular design and virtual screening: The central control system calls the internally pre-trained GAN-Transformer model to generate a set of candidate antimicrobial peptide sequences based on the input target requirements. Control commands are sent to the AI molecular design and virtual screening unit to start the high-throughput molecular synthesis module and the automated molecular interaction analysis module, to perform rapid synthesis and binding kinetics verification of candidate molecules, and to screen out the top N molecules with the highest affinity. Step S2: Design and manufacture of the targeted delivery system: The central control system, based on the selected molecule and the preset application scenario, calls the formulation parameters in the database to determine the carrier type and particle size target; Control commands are sent to the intelligent targeted delivery system fabrication unit to adjust the flow rate ratio and mixing time of each channel of the multi-channel microfluidic chip fabrication platform, and to fabricate nanocarriers loaded with target molecules online. If a multi-layer structure is required, the 3D printing multi-layer capsule molding module is activated to print the nanocarrier and responsive material together. Step S3: Online quality monitoring and closed-loop feedback: The prepared nanocarrier suspension was passed through an online particle size and potential analyzer of a multi-scale online quality monitoring module; If the detected particle size distribution (PDI) is greater than 0.12 or the encapsulation rate is lower than the threshold, the central control system adjusts the flow rate or formulation ratio of the microfluidic chip in real time until the product quality is qualified, thus achieving closed-loop control. Step S4: Simulation and Verification of Biological Effects in the Four Realms Qualified formulation samples are automatically or manually introduced into the corresponding multi-organ on-chip array of the Four Boundary Biological Effects Simulation and Validation Unit; The automated biochemical analyzer automatically samples at preset time points to analyze key biomarkers in the chip's microenvironment; Step S5: Data Integration and Model Iteration The central control system integrates all the data generated in steps S1 to S4 and stores it in the database. Using this data, the digital twin model and reinforcement learning model in the central control server are retrained to optimize the next molecular design scheme and process parameters, achieving intelligent iteration throughout the entire process.
[0025] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.
Claims
1. Intelligent manufacturing equipment for a multi-biological targeted nutritional protection compound preparation, comprising: Manufacturing shell (1), characterized in that the interior of the manufacturing shell (1) is provided with an AI molecular design and virtual screening unit (23), an intelligent targeted delivery system preparation unit (24), a multi-scale online quality monitoring module, a four-dimensional biological effect simulation and verification unit (26), and a central control and digital twin server (25). Among them, the four-dimensional biological effect simulation and verification unit (26) includes a multi-organ chip array, an automated biochemical analyzer, and a fine-tuning module; The fine-tuning module includes a position adjustment component and an axis limiting component; The position adjustment component includes a mounting slot (2) opened on the multi-organ chip array. The mounting slot (2) is symmetrically provided with elastic positioning rods (3). The upper surface of the elastic positioning rods (3) is attached to a moving plate (4). The two moving plates (4) are attached to both sides of the moving frame (5). The surfaces of the two moving frames (5) are engaged with a pull plate (6). The surface of the pull plate (6) is threaded with a threaded rod (7). A drive source is provided on one side of the threaded rod (7). The surface of the moving frame (5) is fixedly connected with a pointer (8).
2. The intelligent manufacturing equipment for a multi-biological targeted nutritional protection compound preparation according to claim 1, characterized in that, The position adjustment assembly also includes magnet blocks (9) fixedly connected to both sides of the lower surface of the movable plate (4). The lower surface of the magnet blocks (9) is attached to an electromagnet (10) connected to an external power source, and the electromagnets (10) are fixedly connected in a rectangular array inside the mounting groove (2).
3. The intelligent manufacturing equipment for a multi-biological targeted nutritional protection compound preparation according to claim 1, characterized in that, The position adjustment component also includes a magnifying glass (11) disposed above the pull plate (6) and perpendicular to the pointer (8). A scale plate (12) is fixedly connected to one side of the magnifying glass (11) for magnifying the pointer (8) and the scale on the scale plate (12). A support frame (13) is fixedly connected to one side of the scale plate (12), and the moving plate (4) is fixedly connected to the support frame (13).
4. The intelligent manufacturing equipment for a multi-biological targeted nutritional protection compound preparation according to claim 3, characterized in that, The axis limiting assembly includes a guide box (14) fixedly connected to one side of the support frame (13). The guide box (14) has radial fine-tuning rollers (15) evenly arranged longitudinally inside. The guide box (14) has a sliding block (16) that is in contact with the radial fine-tuning rollers (15) inside. The sliding block (16) is made of elastic material and is used to fit tightly against the inner wall of the guide box (14).
5. The intelligent manufacturing equipment for a multi-biological targeted nutritional protection compound preparation according to claim 4, characterized in that, The axis limiting assembly also includes a microfluidic sampling needle (17) fitted inside the sliding block (16) and connected to the automated biochemical analyzer. A guide tube (18) is sleeved on the surface of the microfluidic sampling needle (17), and an elastic ring (19) that fits tightly against the outer arc surface of the microfluidic sampling needle (17) is fixedly connected inside the guide tube (18). The guide tube (18) is fixedly connected to the support frame (13).
6. The intelligent manufacturing equipment for a multi-biological targeted nutritional protection compound preparation according to claim 5, characterized in that, The axis limiting assembly also includes a damping spring assembly (20) attached to the lower surface of the sliding block (16). The lower surface of the damping spring assembly (20) is fixedly connected to the guide tube (18), and one side of the damping spring assembly (20) is fixedly connected to an electric push rod (21) fixedly connected to the support frame (13) for driving the reciprocating motion of the sliding block (16) and the microfluidic sampling needle (17).
7. The intelligent manufacturing equipment for a multi-biological targeted nutritional protection compound preparation according to claim 5, characterized in that, A rubber sealing gasket (22) is fixedly connected to one side of the upper surface of the support frame (13) and is coaxially arranged with the microfluidic sampling needle (17). The microfluidic sampling needle (17) can penetrate the rubber sealing gasket (22) and the support frame (13) to pierce into the multi-organ chip array for sampling.
8. The intelligent manufacturing equipment for a multi-biological targeted nutritional protection compound preparation according to claim 1, characterized in that, The AI molecular design and virtual screening unit (23) includes a high-throughput molecular synthesis module and an automated molecular interaction analysis module; Among them, the high-throughput molecular synthesis module contains multiple parallel microreactor arrays, each microreactor being connected to multiple precursor compound tanks, used to automatically synthesize candidate antimicrobial peptide molecules generated by AI models under the instructions of the central control system; Automated molecular interaction analysis module: A microfluidic chip equipped with a surface plasmon resonance sensor is used to automatically detect the binding kinetic constants of candidate molecules and multi-boundary biological target proteins pre-immobilized in the chip channels; The intelligent targeted delivery system fabrication unit (24) includes a multi-channel microfluidic chip fabrication platform and a 3D printing multilayer capsule molding module; Among them, the multi-channel microfluidic chip fabrication platform includes a replaceable microfluidic chip, on which multiple micromixers and microreaction chambers are integrated. The platform is connected to the carrier material storage tank and the core molecule storage tank through a precision injection pump and a pressure controller. 3D Printing Multilayer Capsule Molding Module: Includes a coaxial 3D bioprinter, used to print prepared nanocarriers and hydrogel materials with different pH responses into composite formulations with multilayer structures according to a preset 3D model.
9. The intelligent manufacturing equipment for a multi-biological targeted nutritional protection compound preparation according to claim 1, characterized in that, The multi-scale online quality monitoring module includes an online particle size and potential analyzer and a process analysis technology system. Among them, by connecting the flow cell to the outlet of the microfluidic chip fabrication platform, the particle size distribution and zeta potential of the fabricated nanocarrier are monitored in real time using the principle of dynamic light scattering; Process analysis technology system: includes multiple near-infrared spectral probes installed in key locations such as microfluidic chips and mixing vessels to monitor changes in chemical composition during the reaction process in real time; The multi-organ chip array includes parallel microfluidic cell culture chips that respectively simulate human intestinal epithelium, plant leaf microenvironment, and soil microbial community. The chips are equipped with pH and dissolved oxygen sensors. The automated biochemical analyzer automatically collects samples from the outlet of the multi-organ chip array via a microfluidic sampling needle (17) and connects to the built-in ELISA analysis module for detecting cytokines and metabolites. The central control and digital twin server (25) includes a high-performance computing server on which a digital twin model and AI algorithm are running. The server is connected to the sensors and actuators of all the above units via data cables to form a complete industrial Internet of Things system.
10. A method for intelligent manufacturing equipment of a multi-biological targeted nutritional protection compound preparation, applied to the intelligent manufacturing equipment of the multi-biological targeted nutritional protection compound preparation according to any one of claims 1-9, characterized in that, Includes the following steps: Step S1: Molecular design and virtual screening: The central control system calls the internally pre-trained GAN-Transformer model to generate a set of candidate antimicrobial peptide sequences based on the input target requirements. Control commands are sent to the AI molecular design and virtual screening unit to start the high-throughput molecular synthesis module and the automated molecular interaction analysis module, to perform rapid synthesis and binding kinetics verification of candidate molecules, and to screen out the top N molecules with the highest affinity. Step S2: Design and manufacture of the targeted delivery system: The central control system, based on the selected molecule and the preset application scenario, calls the formulation parameters in the database to determine the carrier type and particle size target; Control commands are sent to the intelligent targeted delivery system fabrication unit to adjust the flow rate ratio and mixing time of each channel of the multi-channel microfluidic chip fabrication platform, and to fabricate nanocarriers loaded with target molecules online. Step S3: Online quality monitoring and closed-loop feedback: The prepared nanocarrier suspension was passed through an online particle size and potential analyzer of a multi-scale online quality monitoring module; If the detected particle size distribution (PDI) is greater than 0.12, the central control system adjusts the flow rate or formulation ratio of the microfluidic chip in real time until the product quality is qualified, thus achieving closed-loop control. Step S4: Simulation and Verification of Biological Effects in the Four Realms Qualified formulation samples are automatically or manually introduced into the corresponding multi-organ on-chip array of the Four Boundary Biological Effects Simulation and Validation Unit; The automated biochemical analyzer automatically samples at preset time points to analyze key biomarkers in the chip's microenvironment; Step S5: Data Integration and Model Iteration The central control system integrates all the data generated in steps S1 to S4 and stores it in the database. Using this data, the digital twin model and reinforcement learning model in the central control server are retrained to optimize the next molecular design scheme and process parameters, achieving intelligent iteration throughout the entire process.